Study On Relationship Between Interleukin-23 And Asthma In Children

Bronchial asthma is one of the most common chronic respiratorytract diseases characterized by reversible airway obstruction,inflammation and airway remodeling. Patients may show thesymptoms as follows: recurrent gasping, dyspnoea, chest distress orcoughing. Status asthmaticus may occur in more serious patients,even threat to their lives. The pathogenesy of asthma is multiple,heredity, respiratory infection, nerves and mind factor, environment,movement, drug and abnormal immune response are all concernedwith asthma. Among them, the abnormal immune response andallergy are the critical factors. The allergy results fromdisequilibrium of Th1/Th2. Interleukin -12(IL-12) is a receivedcytokine which can affect Th cell differentiation and play aprotective part in asthma. Some reports consider that interleukin-23(IL-23) which shares the same subunit p40 with IL-12 possessesbiological activities on T cells that are similar to those of IL-12. It isnow clear that IL-23 plays a key role in autoimmune destruction insome Th1-dominant autoimmunity diseases. So some scholars comeup with the view that the features attributed to IL-12 and TH1development in inflammation are, in fact, dependent on IL-23 andnot on IL-12. If so, IL-23 shall play a protective role in asthma sinceIL-12 is a protective cytokine in asthma and asthma is aTh2-dominant disease. On the other hand, IL-23 can enhance theproduction of proinflammatory factor such as IL-17 and effect onantigen presenting cell (APC) such as dendritic cell (DC) andmacrophage(MP). So IL-23 may also have the function of promotinginflammation development. Then, what role does IL-23 play inasthma after all? The objective of our experiment is to approach therole of IL-23 in children asthma.We selected 63 asthmatic children who came to our hospital fordiagnose and therapy as asthma group and they are all initialtreatment cases who didn't receive hormonal therapy before. Amongthem, there are 52 cases who received inhalation hormonal therapyregularly after final diagnosis. At the same time, we random select65 healthy children who were the same age to asthmatic children ascontrol group. The levels of IL-23 in serum of asthmatic childrenbefore, after glucocorticosteroid treatment and normal children wasexamined with sandwich ELISA methods. Compare the serum IL-23levels of asthma group with normal control group, and asthma groupbefore glucocorticosteroid treatment with the group after treatmentwith statistics software SPSS. The results suggest that the levels ofIL-23 in asthmatic children are higher than that in healthy children,and the IL-23 levels in asthmatic children after glucocorticosteroidtreatment are lower than before glucocorticosteroid treatment. Thereare both significant deferences between the pairs(P<0.001). So wedraw a conclusion that IL-23 involves in asthma pathogenesy and itseffect of promoting inflammation development could be preventedby glucocorticosteroid.IL-23 composed of two subunits p19 and p40 was discovered in2000 in which p40 is the same as p40 in IL-12. p19 is a novelcytokine derived of members of the interleukin-6 (IL-6) helicalcytokine family. The p19 cDNA sequences encode 189/196 aminoacid polypeptides (human and mouse, respectively) corresponding tomature proteins with calculated molecular weights of 18.7 and 19.8kDa. In mouse p19 mRNA present in various tissues and cell typesand in polarized Th1 cells and activated macrophages the highestmRNA levels were found. Both mouse and human dendritic cellsderived from peripheral blood monocytes express high levels of p19mRNA, too. IL-23 responses through binding to the receptors(R)expressing on corresponding cells. IL-23 receptor consists of IL-12Rβ1 in IL-12R and a novel subunit "IL-23R", a member of thehemopoietin receptor family. Human IL-23R is expressed by both Tcells and NK cells, including NKL cells.During the past a few years, we have discovered that IL-23have many biological functions. In humans, IL-23 leads to modestIFN-γ production by na?¨ve and memory T cells;murine IL-23induces strong proliferation of memory T cells;IL-23 can activateThIL-17 cells for production of the proinflammatory cytokine IL-17;IL-23 acts on DC and MP in an autocrine manner since there areIL-23R in these cells. Multiple functions of IL-23 decide itsparticipation in many diseases. IL-23 has anti-tumor and anti-transferactivity. Its effects in autoimmune diseases attract a lot of scholars'attentions, these diseases include experimental allergicencephalomyelitis, collagen-induced arthritis and inflammatorybowel disease. It is now clear that IL-23 has key roles inautoimmune destruction in these diseases. IL-23 also has the activityof inducing inflammation responseness in psoriasis vulgaris which isa chronic inflammatory skin disease mediated byIFN-gamma-expressing type 1 memory T cells. In addition, IL-23plays a part against pathogen infections such as hepatitis C virusinfection, Klebsiella pneumoniae infection, salmonellosis,Cryptococcus neoformans infection, tuberculosis and toxoplasmosis.The results of our experiment indicate that IL-23 can induceinflammation development in asthma pathogenesy. According to thebiological function of IL-23, we presume the mechanism of IL-23 inasthma pathogenesy as follows: ①IL-23 drives the development ofautoreactive IL-17-producing T cells,i.e. ThIL-17 and promoteschronic inflammation dominated by IL-17, IL-6, IL-8 and tumornecrosis factor(TNF) as well as neutrophils and monocytes;②whenthe asthma patients who have formed Th2 cellullar immunologicresponse contact allogeneic antigen again, memory T cells willproliferate because of the activation of IL-23 and secrete Th2cytokines again, thereby secondary immune response is induced andthe gasping attacks;③IL-23 enhances the antigen presentation ofAPCs and exerts biological activities on MP in autocrine manner toproduce interleukin-1(IL-1) and TNF-α which are bothproinflammatory cytokines. But IL-23 has some other biologicalfeatures attributed to inhibiting inflammation in theory. For example,IL-23 may induce TH1 development and the production of IL-12,IFN-γand IL-10 that are contributed to inhibiting inflammation inasthma. So it is necessary for us to carry out more experiments toresearch the effect of IL-23 in asthma. According to incompleteretrieval, there is no report about relationship between IL-23 andasthma. We get the elementary message about the role of IL-23 inasthma through the way of detecting the levels of serum IL-23 inasthmatic and healthy children. But we have to study deep tounderstand its mechanism of action accordingly we could offer thetheoretical evidence and experimental support for new therapia.